Gemcitabine in Non-Small Cell Lung Cancer (NSCLC)

The role of chemotherapy in the treatment of non-smallcell lung cancer (NSCLC) has increased greatly in the past fewyears. While cytotoxic drugs are currently used both as singleagents and in combination for palliation in locally advanced andmetastatic disease, they have also been incorporated intomulti-modality treatment strategies of Stage I to Stage IIINSCLC. One of the main reasons for the increased acceptance ofchemotherapy is the development of new substances.Among the most promising of these new drugs is theantimetabolite gemcitabine. Several single-arm gemcitabine PhaseII studies involving more than 400 patients show validatedresponse rates in more than 20% of the patients. Thesepositive results have also been confirmed in randomized Phase IIstudies. Gemcitabine's unique mechanism of action, its lack ofoverlapping toxicity with other agents, and its favorabletoxicity profile also define it as an ideal candidate forcombination therapy.The activity seen with single-agent gemcitabine therapy canbe compared with that of cisplatin-etoposide combination therapy.Gemcitabine-cisplatin combination response rates range from31% to 54%, with a median survival time between 8.4and 15.4 months and a 1-year survival rate between 30% and59%. In addition to the clinical research ofgemcitabine-cisplatin combinations, gemcitabine has also beentested in various double and triple combinations withcarboplatin, paclitaxel, docetaxel, vinorelbine, and ifosfamide.Investigations combining gemcitabine with radiation therapy areon-going. The following review will summarize results fromrepresentative Phase I/II and III studies using gemcitabine forNSCLC patients.